I can remember when the name for this department was generated. I was
sitting at lunch in the NIH Cafeteria with Dr. Joel Solomon who, at the
time, was on detail here. He was detailed from the FDA (Food and Drug
Administration). Dr. Harvey Alter was also there. I think there were the
three of us. There might have been one more person. Unfortunately, I do
not remember. We were tossing around names that might better reflect the
mission of the department.

“Transfusiology” had been suggested–the Russians used
a similar word–and that seemed somewhat pretentious and difficult
to get out. After a number of different ideas, Transfusion Medicine seemed
to fit the bill, and so we changed the name.

Harden: I am very glad to know that story. Dennis, do you have anything
else you wanted to ask about the pre-AIDS period?

Klein: I am interested in the TTV, and the chimp breeding colony.
But I imagine when we start talking about AIDS you will tell us more about
these.

Klein: I will. Actually, again, I can remember exactly when the name
TTV was generated. It was at a meeting of contractors and contractees–I
guess I was the contractor since I was with the Institute–in Los
Angeles, California. Dr. James Moseley, who was an epidemiologist concentrating
on hepatitis, had gotten the multicenter contract. When we were trying
to determine what to call it, as the contract was for post-transfusion
hepatitis, Jim said, “There are probably a lot of other viruses,
certainly a lot of other viruses. Let’s call it the ‘Transfusion-Transmitted
Virus Study’ instead of the ‘Post-Transfusion Hepatitis Study.’”
Of course, AIDS was not even in anyone’s mind then, but cytomegalovirus
was being thought of, and we were certain that there were other viruses
that were transmitted by blood.

Part of that study was to freeze away specimens for posterity, and a
big part of the contract was, in fact, the freezing facility for keeping
those specimens from donated blood and from patients who had been subsequently
tested. Those specimens are still available, by the way, so if you want
to go back to the 1973-1980 period and find out if an agent was in the
U.S. blood supply, you can still pull some matched sera, and see if a
donor and a recipient had the virus–if the recipient was negative
prior to the transfusion and the donor was positive and then the recipient
became positive after the transfusion–because those specimens are
still frozen.

Harden: That is quite a resource.

Klein:
It was an enormous resource, and it was an enormous battle, as you might
imagine, to get the money to do that study. The only reason that we could
do it, I think, is that at the time the hepatitis rates were in the range–no
one was really sure, and that is why it was a prospective study–but
they were felt to be in the range of 20 to 30 percent. Today, with hepatitis
rates probably below 2 percent, a proposal to fund a prospective post-transfusion
study was discontinued about two years ago. Everyone had submitted proposals
but the money was not there because it looked as if it was not a big enough
national problem to merit the several million dollars that it would have
cost to run the study.

Harden: We should actually do a whole interview about the Clinical Center’s
involvement in hepatitis.

Klein: But that is another day?

Harden: Yes, but let us try to get to the beginning of AIDS. Can you
recall when you first became aware of a problem? Some people heard others
talk about it at hematology meetings in 1979 and 1980. Other people were
not aware of it until 1982 or so. When did you first become aware of AIDS?

Klein: I had not heard of it at hematology meetings at all. In fact,
I think I first became aware of AIDS in 1981 when Dr. Clifford Lane who
was a Clinical Associate in NIAID at the time, began to bring in some
unusual patients with curious immunologic deficits for study under one
of Dr. Anthony (Tony) Fauci’s protocols. It was not called AIDS
at the time. It was a rare disease. It had cellular and humoral immunity
defects. Since Cliff and Tony were interested in these defects, they were
importing patients from San Francisco, Chicago, and Los Angeles, places
that eventually became the hot spots for AIDS.

I remember specifically–and I think this was either in late 1981
or early 1982–that Cliff came down and he wanted us to collect some
white cells from these patients. We had the instruments to do it, so we
could collect concentrates of white cells for laboratory research from
these patients, many of whom had relatively low white blood cell counts.
But we could put them on an instrument for a couple of hours and collect
large numbers of cells.

Harden: Could you give me more details. Did you go to the patients’
hospital rooms, or did they come down here?

Klein: No. They came down here.

Harden: Just like the donors?

Klein: Like the donors, but we had a separate area for patients. We tried
to keep our patients and donors separated. I can remember when we saw
these patients, of course, nobody knew what kind of disease they had,
or how it was acquired. It appeared to be acquired–because the people
we were seeing were adults–but how it was acquired was simply not
known. An infectious etiology was certainly a possibility, and we were
thinking about this possibility at the time, although it was not by any
means at the top of the list. I know many people knew it all along, as
I hear now in 1992 and 1993, but we did not. On the other hand, we took
great precautions with our staff.

Harden: I would like you to talk about that too.

Klein: Yes. Our staff did not wear masks, but they were all gowned and
gloved, which was very unusual at the time. It was not just for those
patients, but also for some of the other unusual patients we saw in the
Clinical Center when we were not exactly sure what they had.

By, I guess it was, late 1982 or early 1983, when the name AIDS was coined,
I can also remember giving Dr. Ed (Edward) Rall a tour of our facilities.
Ed was a very loyal blood donor, by the way, among other things. We were
giving him a tour, and he walked through the clinic that we had on the
D Corridor. At the time we were getting blood from one of these patients,
and Ed said, “Be very careful about these patients.”

Harden: On whom did the responsibility fall to decide what precautions
the staff would take?

Klein: That was my responsibility at the time. We sat down and we talked
to the staff about potential risk. I must say probably more likely than
I would a year later than that, because I, honestly, in my own mind, was
not convinced that this was a transmissible disease. I did not know. I
felt we ought to be cautions, and so we gowned and gloved.

Harden: Was that the standard procedure for hepatitis?

Klein: If you knew someone had hepatitis, in other areas of the hospital
you were never gowned. But we gowned because with our instruments we could
break seals, we could spray plasma or blood, or, since we were carrying
large volumes of materials in plastic bags, if we dropped them which happened
one time, we could get it all over the place. We insisted that individuals
wear gowns, as well as gloves, and we always did that for the hepatitis
patients too.

Harden: That is very interesting. Let us go back to when you were working
with Dr. Lane, taking white cells from his patients.

Klein: Within the next year–it was either in late 1982 or possibly
early 1983–I think the name of AIDS had been coined by then–we
knew that these patients were severely immunodeficient in both arms of
the immune system. Drs. Lane and Fauci came up with an interesting strategy.
They wanted to know whether they could reconstitute the immune system
of these patients, and, if so, how they might do it. Probably the easiest
way, if you could do it, would be to find identical twins, one of whom
was infected and the other of whom was not infected, and do a bone marrow
transplant. By this means, you could maybe transfer immune cells from
the uninfected identical twin to the infected one.

Cliff came down and asked if we could help. He had lined up the NCI (National
Cancer Institute) people who were doing bone marrow transplants and that
was no problem. He asked whether we could help with reconstitution of
immune cells. I said, “Yes, we could do that. What we could do is
use our cell separating technology to collect large numbers of lymphocytes
from the healthy twin, and then you could reinfuse them into the infected
twin.” Actually this had been done in another instance at NIH years
earlier, before I was here, in only one case that I know of. It was a
case of a child with an inherited severe combined immune deficiency. A
fellow by the name of Fitzpatrick, who was an immunologist here, along
with an NCI investigator by the name of Dr. Jay Freireich, had collected
large numbers of normal lymphocytes to give to a young girl who had a
systemic fungal infection and severe skin disease. She had gotten transient
immune reconstitution.

So, I became an associate investigator
on that protocol, and Cliff, I am sure, has the original protocol that
we used. We got multiple sets of twins and did, in fact, demonstrate that
you could reconstitute these individuals using bone marrow transplants
and multiple collections of lymphocytes–immune white blood cells–from
the healthy individual and putting them back into the infected individual.
However, once you started doing this, they reverted to their former situation
within a matter of months. We published this in the New England Journal
of Medicine.

One thing that this research did suggest to us, again, with other evidence
mounting, was that this was probably an infectious process, and that we
had not got rid of the agent. No matter what you did to reconstitute the
immune system, unless you get rid of the agent from the patient you were
not going to cure the patient. This subsequently resulted in a variety
of modified protocols continuing actually up to the present time, where
the patient is treated with a variety of drugs plus cells from the identical
twin. Cliff would be able to tell you how many there have been. I think
they have had thirty sets of identical twins, one of whom is infected
and the other of whom is not. If you had asked me back in 1982 would there
be that many, I would have said, “This is insane. This will be a
study of two or three sets of twins, if we are lucky.” But in point
of fact, Cliff has had an enormous number of twins who have been involved
in these studies, right up until the present time where we are now growing
the healthy twin’s cells, expanding them in incubators, and giving
them back to the infected twin. The next step may be gene modification
of those cells. So, we have moved from a sort of crude clinical science
to very sophisticated science, immune reconstitution of these patients
using our identical twin adoptive immunotherapy.